{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:58:51Z","timestamp":1790636331726,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471340"],"award-info":[{"award-number":["81471340"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771412"],"award-info":[{"award-number":["81771412"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801149"],"award-info":[{"award-number":["81801149"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971222"],"award-info":[{"award-number":["81971222"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the effect of erythropoietin (EPO) on the differentiation of neural stem cells (NSCs)\/neural progenitors (NPs) in the treatment of hypoxic\u2013ischemic injury and its potential mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fetal NSCs\/NPs were treated with EPO after oxygen and glucose deprivation\/reoxygenation (OGD\/R). Cell viability, proliferation, and differentiation of NSCs\/NPs were detected by CellTiter\u2010Glo, Edu assay, flow cytometry, and quantitative real\u2010time PCR (qPCR). Immunofluorescence staining, co\u2010immunoprecipitation (Co\u2010IP), and western blotting were used to test the existence of EPO receptor\/\u03b2 common receptor (EPOR\/\u03b2CR) heterodimer on NSCs\/NPs and the possible pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EPO treatment at different time points increased cell viability without affecting proliferation. EPO treatment immediately after OGD\/R promoted oligodendrocyte and astrocyte differentiation, while decreasing neuronal differentiation of NSCs\/NPs. EPOR\/\u03b2CR heterodimer existed on the cell surface of the fetal cortical NSCs\/NPs, EPO treatment significantly increased the mRNA expression of \u03b2CR and elevated the correlation between EPOR and \u03b2CR levels. In addition, mass spectrometry analysis identified Syne\u20101 as a downstream signaling molecule of the EPOR\/\u03b2CR heterodimer. Immunofluorescence staining and western blotting indicated that the \u03b2CR\/Syne\u20101\/H3K9me3 pathway was possibly involved in the differentiation of fetal neural stem cells into the glial cell effect of EPO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>EPO treatment immediately after OGD\/R could not facilitate fetal NSCs\/NPs neurogenesis but promoted the formation of the EPOR\/\u03b2CR heterodimer on fetal NSCs\/NPs, which mediates its function in glial differentiation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13876","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T05:59:02Z","timestamp":1655531942000},"page":"1351-1364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Erythropoietin promotes the differentiation of fetal neural stem cells into glial cells via the erythropoietin receptor\u2010\u03b2 common receptor\/Syne\u20101\/<scp>H3K9me3<\/scp> pathway"],"prefix":"10.1111","volume":"28","author":[{"given":"Zhen\u2010Hong","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Cerebrovascular Disease Research Xuanwu Hospital of Capital Medical University  Beijing China"},{"name":"Beijing Geriatric Medical Research Center and National Clinical Research Center for Geriatric Disorders  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Jia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research Xuanwu Hospital of Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010Ping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research Xuanwu Hospital of Capital Medical University  Beijing China"},{"name":"Beijing Geriatric Medical Research Center and National Clinical Research Center for Geriatric Disorders  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1485-4261","authenticated-orcid":false,"given":"Fang\u2010Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research Xuanwu Hospital of Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Tao","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research Xuanwu Hospital of Capital Medical University  Beijing China"},{"name":"Beijing Geriatric Medical Research Center and National Clinical Research Center for Geriatric Disorders  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2712-8974","authenticated-orcid":false,"given":"Yu\u2010Min","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research Xuanwu Hospital of Capital Medical University  Beijing China"},{"name":"Beijing Geriatric Medical Research Center and National Clinical Research Center for Geriatric Disorders  Beijing China"},{"name":"Beijing Institute for Brain Disorders Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong\u2010Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research Xuanwu Hospital of Capital Medical University  Beijing China"},{"name":"Beijing Geriatric Medical Research Center and National Clinical Research Center for Geriatric Disorders  Beijing 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